Long-term Space Research Articles

Release of CD36-associated cell-free mitochondrial DNA and RNA as a hallmark of space environment response

A detailed understanding of how spaceflight affects human health is essential for long-term space exploration. Liquid biopsies allow for minimally-invasive multi-omics assessments that can resolve the molecular heterogeneity of internal tissues. Here, we report initial results from the JAXA Cell-Free Epigenome Study, a liquid biopsy study with six astronauts who resided on the International Space Station (ISS) for more than 120 days. Analysis of plasma cell-free RNA (cfRNA) collected before, during, and after spaceflight confirms previously reported mitochondrial dysregulation in space. Screening with 361 cell surface marker antibodies identifies a mitochondrial DNA-enriched fraction associated with the scavenger receptor CD36. RNA-sequencing of the CD36 fraction reveals tissue-enriched RNA species, suggesting the plasma mitochondrial components originated from various tissues. We compare our plasma cfRNA data to mouse plasma cfRNA data from a previous JAXA mission, which had used on-board artificial gravity, and discover a link between microgravity and the observed mitochondrial responses.

Key Technologies for Korean Space Heat Pipe Reactor

Sustainable energy is crucial for long-term space missions. Fission surface power is a leading option due to its ability to provide consistent electricity and heat irrespective of the sun’s position or distance. A heat pipe is the primary cooling solution for space fission power systems. It operates without the need for additional electricity or gravity. It offers the advantage of streamlining the reactor design by eliminating components such as pumps and piping. This paper presents the advancements in the Korean space heat pipe reactor development program over the past 4 years. The primary objectives of this program include the development of codes for space heat pipe reactors, the innovative design of a hybrid wick structure, and the evaluation of the thermal performance of liquid-metal heat pipes.

Proceeding toward the maximum of solar cycle 25 with a radiation environment similar to the previous cycle

The Sun exhibited lower-than-average activity levels, including a weak maximum and a prolonged minimum in the solar cycle (SC) 24. Thiswas following a 60-year trend of weakening solar activity, leading to speculations that we could be moving into another secular minimum scenario like the Dalton or the Gleissberg periods. During such periods, the fluxes of galactic cosmic rays (GCRs) increase significantly, introducing radiation hazards for long-term crewed space explorations. In our previous work, we predicted the level of solar activity, and thus, the radiation environment for SC25 will be similar to SC24. In this paper, we show that, to date, the radiation environment observed by CRaTER has been similar to SC24, as we predicted. Furthermore, we predict that if the radiation environment remains similar to SC24, the maximum value for permissible mission duration (PMD) for SC25 will be 917-230+234 days based on NASA’s latest permissible exposure limit (PEL).

Exploiting the Unique Biology of Caenorhabditis elegans to Launch Neurodegeneration Studies in Space.

The 21st century is likely to be the first century in which large-scale short- and long-term space missions become common. Accordingly, an ever-increasing body of research is focusing on understanding the effects of current and future space expeditions on human physiology in health and disease. Yet the complex experimental environment, the small number of participants, and the high cost of space missions are among the primary factors that hinder a better understanding of the impact of space missions on human physiology. The goal of our research was to develop a cost-effective, compact, and easy-to-manipulate system to address questions related to human health and disease in space. This initiative was part of the Ramon SpaceLab program, an annual research-based learning program designed to cultivate high school students' involvement in space exploration by facilitating experiments aboard the International Space Station (ISS). In the present study, we used the nematode Caenorhabditis elegans (C. elegans), a well-suited model organism, to investigate the effect of space missions on neurodegeneration-related processes. Our study specifically focused on the level of aggregation of Huntington's disease-causing polyglutamine stretch-containing (PolyQ) proteins in C. elegans muscles, the canonical system for studying neurodegeneration in this organism. We compared animals expressing PolyQ proteins grown onboard the ISS with their genetically identical siblings grown on Earth and observed a significant difference in the number of aggregates between the two populations. Currently, it is challenging to determine whether this effect stems from developmental or morphological differences between the cultures or is a result of life in space. Nevertheless, our results serve as a proof of concept and open a new avenue for utilizing C. elegans to address various open questions in space studies, including the effects of space conditions on the onset and development of neurodegenerative diseases.

Enhanced UV photodetection in SnO2 microwire arrays (MWAs) thin films by γ-ray irradiation

In this study, the gamma ray irradiation-induced photoelectric responses of SnO2 microwire arrays (MWAs) UV photodetectors were investigated and compared with the unirradiated state. The corresponding surface morphology, crystal structure, and XPS spectrum were analyzed. Results indicated that low doses (≤500krad) of gamma ray irradiation led to enhanced photocurrent and responsivity, whereas high doses resulted in significant degradation of the photoelectric response. At a radiation dose of 300krad, a photocurrent of 264 μA and a responsivity of 1.83 A/W were realized under 365 nm UV light illumination at a bias voltage of 5 V. These values represent an increase of 34.6 % and 44.1 %, respectively, compared with the unirradiated sample. Surprisingly, the fabricated SnO2 MWAs UV photodetectors demonstrated resilience to gamma ray irradiation doses up to 500krad, which is equivalent to the radiation dose accumulated by satellites in low-Earth orbit over 20 years. Our findings suggested that the fabricated SnO2 microwire arrays (MWAs) UV detector has the potential to be used for long-term space missions.

AOP report: Development of an adverse outcome pathway for deposition of energy leading to cataracts.

Cataracts are one of the leading causes of blindness, with an estimated 95 million people affected worldwide. A hallmark of cataract development is lens opacification, typically associated not only with aging but also radiation exposure as encountered by interventional radiologists and astronauts during the long-term space mission. To better understand radiation-induced cataracts, the adverse outcome pathway (AOP) framework was used to structure and evaluate knowledge across biological levels of organization (e.g., macromolecular, cell, tissue, organ, organism and population). AOPs identify a sequence of key events (KEs) causally connected by key event relationships (KERs) beginning with a molecular initiating event to an adverse outcome (AO) of relevance to regulatory decision-making. To construct the cataract AO and retrieve evidence to support it, a scoping review methodology was used to filter, screen, and review studies based on the modified Bradford Hill criteria. Eight KEs were identified that were moderately supported by empirical evidence (e.g., dose-, time-, incidence-concordance) across the adjacent (directly linked) relationships using well-established endpoints. Over half of the evidence to justify the KER linkages was derived from the evidence stream of biological plausibility. Early KEs of oxidative stress and protein modifications had strong linkages to downstream KEs and could be the focus of countermeasure development. Several identified knowledge gaps and inconsistencies related to the quantitative understanding of KERs which could be the basis of future research, most notably directed to experiments in the range of low or moderate doses and dose-rates, relevant to radiation workers and other occupational exposures.

Proteomic and phosphoproteomic characterization of cardiovascular tissues after long term exposure to simulated space radiation.

Introduction: It may take decades to develop cardiovascular dysfunction following exposure to high doses of ionizing radiation from medical therapy or from nuclear accidents. Since astronauts may be exposed continually to a complex space radiation environment unlike that experienced on Earth, it is unresolved whether there is a risk to cardiovascular health during long-term space exploration missions. Previously, we have described that mice exposed to a single dose of simplified Galactic Cosmic Ray (GCR5-ion) develop cardiovascular dysfunction by 12months post-radiation. Methods: To investigate the biological basis of this dysfunction, here we performed a quantitative mass spectrometry-based proteomics analysis of heart tissue (proteome and phosphoproteome) and plasma (proteome only) from these mice at 8months post-radiation. Results: Differentially expressed proteins (DEPs) for irradiated versus sham irradiated samples (fold-change ≥1.2 and an adjusted p-value of ≤0.05) were identified for each proteomics data set. For the heart proteome, there were 87 significant DEPs (11 upregulated and 76 downregulated); for the heart phosphoproteome, there were 60 significant differentially phosphorylated peptides (17 upregulated and 43 downregulated); and for the plasma proteome, there was only one upregulated protein. A Gene Set Enrichment Analysis (GSEA) technique that assesses canonical pathways from BIOCARTA, KEGG, PID, REACTOME, and WikiPathways revealed significant perturbation in pathways in each data set. For the heart proteome, 166 pathways were significantly altered (36 upregulated and 130 downregulated); for the plasma proteome, there were 73 pathways significantly altered (25 upregulated and 48 downregulated); and for the phosphoproteome, there were 223 pathways significantly affected at 0.1 adjusted p-value cutoff. Pathways related to inflammation were the most highly perturbed in the heart and plasma. In line with sustained inflammation, neutrophil extracellular traps (NETs) were demonstrated to be increased in GCR5-ion irradiated hearts at 12-month post irradiation. NETs play a fundamental role in combating bacterial pathogens, modulating inflammatory responses, inflicting damage on healthy tissues, and escalating vascular thrombosis. Discussion: These findings suggest that a single exposure to GCR5-ion results in long-lasting changes in the proteome and that these proteomic changes can potentiate acute and chronic health issues for astronauts, such as what we have previously described with late cardiac dysfunction in these mice.

Transcriptome sequencing reveals the promotion of apoptosis and M1 polarization of microglia under simulated microgravity

The exponential progress in the field of space science and technology has facilitated the prolonged habitation of astronauts in the space environment. However, the neurological and cognitive impairments of astronauts have become major factor that directly impede the successful completion of space missions. Studies have demonstrated that microgravity can diminish neuronal functions and cognitive abilities by altering the microenvironment of the brain (BME). Microglia, vital immune cells responsible for regulating the integrity of the blood-brain barrier, have been identified as the principal contributing elements to the neurological deterioration observed in microgravity conditions. The primary objective of this study was to provide an understanding of the molecular processes underlying the behavior of microglia under conditions of microgravity. Using a Random Positioning Machine (RPM) to simulate microgravity, our study found that microgravity reduces BV2 microglial cell viability, induces M1 polarization, and significantly increases late apoptosis. Transcriptome analysis revealed 142 differentially expressed genes related to microglial phenotype and inflammation, with qPCR validating selected DEGs. These results elucidate the molecular mechanisms of microglial behavior under microgravity, highlighting gene expression changes and cellular damage. This study provides a conceptual framework for comprehending the influence of microgravity on the neurological system, establishing countermeasures against functional damage to the nervous system caused by space flight, and serving as a reference for future deep space exploration and long-term manned space medical support.

Study on the single event reliability of a Pavlov system based on neuron chip

Artificial intelligence (AI) system based on neuron chip with high reliability and low power-consumption is of great importance for long-term space mission and deep space exploration. However, the AI application is challenged by the single event effect of microelectronics including soft error and hard damage upon harsh space radiation. In this work, an AI modelled Pavlov system based on a mixed-signal spike neuron chip has been studied at unit and chip level in response to single event transient injections. The heavy ion beam and laser irradiation were performed to evaluate the single event reliability of the neuron system. The results indicate that the Pavlov neuron chip possesses excellent single event effect immunity and high reliability to space radiation. This work demonstrates that the AI system based on neuron chip is reliable for robotic and unmanned application with space radiation and nuclear exposure environments.

Highly sensitive detection of the neurodegenerative biomarker Tau by using the concentration effect of the pyro-electrohydrodynamic jetting

It is largely documented that neurodegenerative diseases can be effectively treated only if early diagnosed. In this context, the structural changes of some biomolecules such as Tau, seem to play a key role in neurodegeneration mechanism becoming eligible targets for an early diagnosis. Post-translational modifications are responsible to drive the Tau protein towards a transition phase from a native disorder conformation into a preaggregation state, which then straight recruits the final fibrillization process. Here, we show for the first time the detection of pre-aggregated Tau in artificial urine at femto-molar level, through the concentration effect of the pyro-electrohydrodynamic jet (p-jet) technique. An excellent linear calibration curve is demonstrated at the femto-molar level with a limit of detection (LOD) of 130 fM. Moreover, for the first time we show here the structure stability of the protein after p-jet application through a deep spectroscopic investigation. Thanks to the small volumes required and the relatively compact and cost-effective characteristics, this technique represents an innovative breakthrough in monitoring the early stage associated to neurodegeneration syndromes in different scenarios of point of care (POC) and such as for example in long-term human space exploration missions.

In-orbit dark count rate performance and radiation damage high-temperature annealing of silicon avalanche photodiode single-photon detectors of the Micius satellite.

Silicon avalanche photodiode (APD) single-photon detectors in space are continuously affected by radiation, which gradually degrades their dark count performance. From August 2016 to June 2023, we conducted approximately seven years (2507 days) of in-orbit monitoring of the dark count performance of APD single-photon detectors on the Micius Quantum Science Experimental Satellite. The results showed that due to radiation effects, the dark count growth rate was approximately 6.79 cps/day @ -24 °C and 0.37 cps/day @ -55 °C, with a significant suppression effect on radiation-induced dark counts at lower operating temperature. Based on the proposed radiation damage induced dark count annealing model, simulations were conducted for the in-orbit dark counts of the detector, the simulation results are consistent with in-orbit test data. In May 2022, four of these detectors underwent a cumulative 5.7 hours high-temperature annealing test at 76 °C, dark count rate shows no measurable changes, consistent with annealing model. As of now, these ten APD single-photon detectors on the Micius Quantum Science Experimental Satellite have been in operation for approximately 2507 days and are still functioning properly, providing valuable experience for the future long-term space applications of silicon APD single-photon detectors.

Closing the loop in space 3D printing: Effect of vacuum, recycling, and UV aging on high performance thermoplastics produced via filament extrusion additive manufacturing

The outlook for space exploration, and the long-term sustainable presence of humans in space, rely upon the advancement of in-situ manufacturing capabilities. In-space additive manufacturing (AM) has gained significant attention due to its potential to produce spare parts in-situ and facilitate repairs for extending space missions. However, to date, there is no AM system capable of processing high-performance engineering thermoplastic polymers within uncontrolled space conditions (i.e., reduced gravity, vacuum, and radiation environment). Additionally, the effect of ultra-violet (UV) radiation on printed parts has remained unexplored. In this work, a custom-built filament extrusion AM breadboard has been developed and tested enabling the fabrication of engineering thermoplastic polymers, whereby the machine was placed inside a vacuum chamber to partly mimic the harsh space environment. Mechanical (tensile and flexural) and thermal (thermogravimetric analysis, differential scanning calorimetry and dynamic mechanical analysis) tests were conducted on the printed specimens before and after exposure to UV aging. Moreover, the printed geometries underwent a recycling process involved the shredding of the pristine 3D-printed polymeric samples, the drying of the obtained granulates and finally the extrusion of 3D-printable filaments. The polymeric recycled 3D-printed specimens were then subjected to further mechanical and thermal testing, offering valuable insights into the feasibility of in-space AM and the potential to augment the circularity of the printed parts. The results of the mechanical and thermal tests, together with the effect of vacuum printing, UV aging, and recycling, are provided within the manuscript. This work cements the basic building blocks to sustainably advance on-orbit and in-space infrastructure, and paves the way for long-term human space missions.

Three-Dimensional Particle Tracing Analysis of a Rotational Magnetic Sail

A magnetic sail is a propellantless propulsion system that has great potential in long-term space travel. It utilizes the interaction between the solar wind and the magnetic field generated by a high-current coil. However, the requirement of a large-sized coil with a high working current limits its practical application. To reduce the coil size while maintaining the thrust, a rotational magnetic sail is proposed and analyzed using the three-dimensional particle tracing method. The results show that the magnetic sail thrust significantly increases with the rotational speed and is influenced by plasma parameters. Moreover, the sail achieves the maximum thrust and the most stable attitude when the magnetic moment vector is perpendicular to the particle impact direction. The analysis implies that the rotational magnetic sail can shrink to about a minimum of 20% and approximately 1% of the size of a static magnetic sail in the solar wind and low Earth orbit, respectively, while maintaining the same thrust.

Thermal and Electrical Performance Analyses of a 100-W Radioisotope Thermoelectric Generator for Space Exploration

A 100-W radioisotope thermoelectric generator (RTG) is by far the most suitable power supply for long-term deep space exploration where solar power would not be feasible. Understanding the thermal performance and electrical performance of the RTG under operational conditions is paramount for its nominal and safety performance during the space mission. In this paper, modeling and experimental studies on the thermal behavior and electrical performance of the 100-W RTG have been conducted. The RTG uses high conversion efficiency skutterudite-based thermoelectric convertor (TEC) arrays thermally coupled with a radioisotope heat unit (RHU) to generate electricity. A comprehensive finite element model and an electrical heating prototype of the 100-W RTG have been built to assess the performance of the RTG designs. Critical temperature, generated power, and energy conversion efficiency were evaluated. The simulation results show that the maximum output power of the RTG can reach about 120 W(electric); the temperature of the hot end of the TECs is about 853 K, and the temperature of the cold end is about 473 K, making a temperature difference of about 380 K. The RTG prototype with Bi2Te3 TECs generated about 60 W(electric) of electrical power in the first experimental research stage. These research results have significant reference for extension of the RTG prototype to the actual power source of the RHU and allow for future research and development improvements of the 100-W RTG.

Whole-transcriptome RNA sequencing reveals CeRNA regulatory network under long-term space composite stress in Rats

To systematically evaluate the effect of simulated long-term spaceflight composite stress (LSCS) in hippocampus and gain more insights into the transcriptomic landscape and molecular mechanism, we performed whole-transcriptome sequencing based on the control group (Ctrl) and the simulated long-term spaceflight composite stress group (LSCS) from six hippocampus of rats. Subsequently, differential expression analysis was performed on the Ctrl and LSCS groups, followed by enrichment analysis and functional interaction prediction analysis to investigate gene-regulatory circuits in LSCS. In addition, competitive endogenous RNA (ceRNA) network was constructed to gain insights into genetic interaction. The result showed that 276 differentially expressed messenger RNAs (DEmRNAs), 139 differentially expressed long non-coding RNAs (DElncRNAs), 103 differentially expressed circular RNAs (DEcircRNAs), and 52 differentially expressed microRNAs (DEmiRNAs) were found in LSCS samples compared with the controls, which were then subjected to enrichment analysis of Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to find potential functions. PI3K-Akt signaling pathway and MAPK signaling pathway may play fundamental roles in the pathogenesis of LSCS. A ceRNA network was constructed with the predicted 340 DE pairs, which revealed the interaction roles of 220 DEmiRNA-DEmRNA pairs, 76 DEmiRNA-DElncRNA pairs, and 44 DEmiRNA-DEcircRNA pairs. Further, Thrombospondins2 was found to be a key target among those ceRNAs. Overall, we conducted for the first time a full transcriptomic analysis of the response of hippocampus to the LSCS that involved a potential ceRNA network, thus providing a basis to study the underlying mechanism of the LSCS.

Молекулярно-генетическое тестирование в контексте медико-биологических рисков здоровью космонавтов

Today, genetic studies yield quite a large amount of information about a person, which, in many cases, allows predicting the risks of certain diseases. This gives grounds to believe that such testing can also be applied in the field of manned spaceflights in order to identify candidates best adapted to specific risks. The article examines publications on genetic polymorphisms and their effects on the carrier phenotype, namely, on such manifestations that are of interest in the context of risks arising during long-term space flights. Specific genes are listed and examples of allelic variants are given. Publications describing new molecular methods of monitoring human health are also considered, biomarkers that can be used for research in the interests of regular examination of active astronauts are identified.

High-altitude balloon platform for studying the biological response of living organisms exposed to near-space environments

The intangible desire to explore the mysteries of the universe has driven numerous advancements for humanity for centuries. Extraterrestrial journeys are becoming more realistic as a result of human curiosity and endeavors. Over the years, space biology research has played a significant role in understanding the hazardous effects of the space environment on human health during long-term space travel. The inevitable consequence of a space voyage is space ionizing radiation, which has deadly aftereffects on the human body. The paramount objective of this study is to provide a robust platform for performing biological experiments within the Earth's stratosphere by utilizing high-altitude balloons. This platform allows the use of a biological payload to simulate spaceflight missions within the unique properties of space that cannot be replicated in terrestrial facilities. This paper describes the feasibility and demonstration of a biological balloon mission suitable for students and scientists to perform space biology experiments within the boundary of the stratosphere. In this study, a high-altitude balloon was launched into the upper atmosphere (∼29 km altitude), where living microorganisms were exposed to a hazardous combination of UV irradiation, ultralow pressure and cold shock. The balloon carried the budding yeast Saccharomyces cerevisiae to investigate microbial survival potential under extreme conditions. The results indicated a notable reduction in biosample mortality two orders of magnitude (2-log) after exposure to 164.9 kJ m−2 UV. Postflight experiments have shown strong evidence that the effect of UV irradiation on living organisms is stronger than that of other extreme conditions.

Water Recovery in Life Support Systems for Long-Term Space Missions

Water Recovery in Life Support Systems for Long-Term Space Missions

Quantitative analysis of change in bone volume 5 years after sinus floor elevation using plate-shaped bone substitutes: a prospective observational study

PurposeTricalcium phosphate (TCP) has osteoconductive ability and reportedly offers similar clinical results as autogenous bone grafts in dental implant treatment. However, few reports quantify temporal changes in augmented bone volume after sinus augmentation. We aimed to establish a three-dimensional (3D) quantification method to assess bone volume after sinus augmentation and to evaluate biocompatibility of the TCP plate.MethodsMaxillary sinus floor augmentation was performed employing the lateral window technique, and plate-shaped β-TCP (TCP plate) was used instead of granular bone grafting materials. After lifting the sinus membrane, the TCP plate was inserted and supported by dental implants or micro-screws. The changes in bone volumes in the maxillary sinus before and after surgery were recorded using cone-beam computed tomography, saved as Digital Imaging and Communications in Medicine-formatted files, and transformed to Standard Triangle Language (STL)-formatted files. Pre- and post-operative STL data of bone volume were superimposed, and the augmented bone volume was calculated. Moreover, changes in bone volumes, TCP plate resorption rates, and bone heights surrounding the implants were three dimensionally quantified.ResultsFifteen implants in nine subjects were included in this study. TCP plates secured long-term space making, with results similar to those of granular bone substitutes. Newly formed bone was identified around the implant without bone graft material. TCP plate was absorbed and gradually disappeared.ConclusionsA novel 3D quantification method was established to evaluate changes in bone volume. Clinical application of TCP plate in sinus augmentation could be a better procedure in terms of prognosis and safety.

Long-term space missions' effects on the human organism: what we do know and what requires further research.

Space has always fascinated people. Many years have passed since the first spaceflight, and in addition to the enormous technological progress, the level of understanding of human physiology in space is also increasing. The presented paper aims to summarize the recent research findings on the influence of the space environment (microgravity, pressure differences, cosmic radiation, etc.) on the human body systems during short-term and long-term space missions. The review also presents the biggest challenges and problems that must be solved in order to extend safely the time of human stay in space. In the era of increasing engineering capabilities, plans to colonize other planets, and the growing interest in commercial space flights, the most topical issues of modern medicine seems to be understanding the effects of long-term stay in space, and finding solutions to minimize the harmful effects of the space environment on the human body.